There is an ongoing need for improved vaccines and vaccine adjuvants, as many existing vaccine formulations developed using conventional methods still present serious risks to patients without providing increased potency. For example, attenuated organisms still present the risks of serious infection to compromised patients, and potent adjuvants such as cholera toxin are too toxic for use in humans. Advances in genomics technologies have enabled a more focused search for gene targets for use in new vaccine development. We have used gene expression profiling of cells and tissue to identify candidate receptors in mucosal immune associated epithelium; several of these appear to be pattern recognition receptors. We propose that Peyer's Patch Follicle Associated Epithelium (FAE) is a specialized sensor for mucosal adjuvant activity using these receptors, and that these receptors are ideal candidates for triggering mucosal immunity. We plan to develop formulations of synthetic ligands to these receptors and ligand-antigen conjugates to test their potency as specific mucosal adjuvants when applied to nasal and intestinal epithelium. These studies will establish a novel adjuvant system that will be useful in generating new formulations of synthetic mucosal vaccines against respiratory agents such as influenza and enteric pathogens such as Salmonella.